Dark side of clinical trials

Kudos to HANS for publishing a series of articles on unethical clinical trials being carried out in India by foreign agencies in general and, in particular, the deaths of girls in tribal schools of Khammam after administering HPV vaccine for clinical trials. As reported, between January 2005 and September 2016, there were several deaths due to the clinical trials, mainly due to the unethical methods employed thereof. 

Human papillomavirus (HPV) is a viral infection that is passed between people through skin-to-skin contact. There are more than 100 varieties of HPV, 40 of which are passed through sexual contact and can affect your genitals, mouth, or throat, according to healthline.com.

HPV virus is found in many people (in America), latent, does not pose any health problem.  It is predominantly is a great risk to those who have a number of sexual partners.  It takes several years for HPV to turn into cancer, the symptoms being cervical cancer of women and genital warts on penis for men. 

There is no treatment to control HPV virus. Vaccines do not treat pre-existing HPV virus. Only in some cases, HPV is blown to cancer for which usual treatment is to be given for cancer treatment, and not for HPV. Further being vaccinated provides no guarantee against cervical cancer. Cervical cancer may occur due to several other reasons, not due to HPV alone. Long-term data is not available for how many years, the vaccine is effective. The efficacy of vaccine will be known after 10, 15 or 20 years after vaccination. Vaccines are to be administered to girls and women between 9 and 16 years before initiation of sexual activity.

Further complications: There are at least 100 types (strains) of HPV. Only two types of strains -16 and 18 – can cause cancer. It is believed that Cervarix® vaccine (GSK manufacturer) protects against type (strains) 16 and 18, while Gardasil vaccine (Merck) provides protection to type 16 ,8 and 11.  Again comparative clinical trials are necessary between these two.  

We believe strongly there is no long-term monitoring programme in these clinical trials at Khammam and Gujarat to evaluate if the girls got cervical cancer or not. If they have such programme, they have to monitor all the 24,000 girls, for a period of 25 years.  

It looks the intention of the funding agency is only short-term to study toxicology aspects of HPV, and side effects, permanent or temporary, only. Still another question is why they have selected remote tribal school children, why not children of international public schoolchildren's in our country? Moreover, there is specific protection is provided in the Constitution for agency tribals in the matter of privacy and property and health care.  Are they violated? 

Several questions, doubts and remedial measures are in sight: First, in ethical committees, usually, a majority of the members are outside experts. They frame guidelines, meet only once.  They lay guidelines as per established protocol, review the results and comment, based on the papers laid on the table.  The ground personnel i.e., doctors, biochemists, pharmacists and the host institute may or may not take these comments. Honesty and  integrity is what is required by those who are 

Another major reason for preferring clinical trials in India is that there are several medical and pharmacy colleges and we have abundant manpower, willing to undertake any study including the questionable clinical trials. Moreover with WTO (World Trade Organisation) liberal policy, it is possible that private hospitals/companies take clinical trials assignment from foreign agencies. There are many companies in Hyderabad itself. 

Most clinical trials assigned to India or other developing countries are for experimental drugs, which may not see the light of the day. Their studies are not useful to improve our health standards in India. As already pointed out, toxicological studies of the drug are the main objective of the sponsors i.e., foreign pharmaceutical companies. 
Therefore, it is advisable that the Government of India should not permit at all any clinical trials. 

The government may accept limited clinical trials by ICMR for those popular drugs which are already available in the West and are necessary for Indians in curing the diseases. Regulatory authority for monitoring clinical studies is a must and ethical committee alone will not serve any purpose. 

Although Indian advisory group on immunisation is in favour of inclusion of HPV vaccination in Indian universal immunization programme (UIP), a writ petition against it, filed by some activists in Supreme Court in 2012, is pending. It is wise to differ this programme at least for 15 years, to know the experience of other countries on this vaccination. There is no hurry to introduce this controversial vaccine.

This controversy on HPV reminds us of the attempts to introduce BCG vaccine for TB in 1950s. in India. (Raja Gopalacharya (Rajaji) former Governor of India) stoutly opposed it due to safety reasons. Thus, the history of the BCG Vaccine nearly came to an end. 

By: Dr K Nagaiah & Prof G Srimannarayana
(Dr Nagaiah is a Chief Scientist with IICT, Hyderabad, and Prof Srimannarayana is a retired Chemistry Professor of Osmania University, Hyderabad)